The classical cannabinoid Δ9-Tetrahydrocannabinol (Δ9-THC) is the major active constituent extracted from Cannabis sativa. The effects of such cannabinoids are due to an interaction with specific GPCR receptors. Presently, two cannabinoid receptors have been characterized: CB1, a central receptor found in the mammalian brain and a number of other sites in peripheral tissues; and CB2, a peripheral receptor found principally in cells related to the immune system. The CB1 receptor is believed to mediate the psychoactive properties associated with classical cannabinoids. Characterization of these receptors has been made possible by the development of specific synthetic ligands such as the agonists WIN 55212-2 and CP 55,940.
In addition to acting at the cannabinoid receptors, cannabinoids such as Δ9-THC also affect cellular membranes, thereby producing undesirable side effects such as drowsiness, impairment of monoamine oxidase function and impairment of non-receptor mediated brain function. The addictive and psychotropic properties of some cannabinoids also limit their therapeutic value.
U.S. Pat. No. 6,028,084 describes some pyrazole derivatives alleged to have binding affinity for the central cannabinoid receptor. International Publication Number WO 01/29007A1 also describes some pyrazole derivatives having binding affinity for cannabinoid receptors.
The pharmacological effects of cannabinoids pertain to a variety of areas such as the central nervous system, the cardiovascular system, the immune system, the reproductive system and/or endocrine system. Compounds possessing an affinity for the CB1 and/or the CB2 cannabinoid receptors are useful as agents acting on the central nervous system and in a variety of other physiological systems.